Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture

Background: The highest incidence of osteoporotic fractures is found in northern Europe, where dietary intake of vitamin A (retinol) is unusually high. In animals, the most common adverse effect of toxic doses of retinol is spontaneous fracture. Objective: To investigate whether excessive dietary intake of vitamin A is associated with decreased bone mineral density and increased risk for hip fracture. Design: A cross-sectional study and a nested case-control study. Setting: Two counties in central Sweden. Participants: For the cross-sectional study, 175 women 28 to 74 years of age were randomly selected. For the nested case-control study, 247 women who had a first hip fracture within 2 to 64 months after enrollment and 873 age-matched controls were selected from a mammography study cohort of 66 651 women 40 to 76 years of age. Measurements: Retinol intake was estimated from dietary records and a food-frequency questionnaire. Bone mineral density was measured with dual-energy x-ray absorptiometry. Hip fracture was identified by using hospital discharge records and was confirmed by record review. Results: In multivariate analysis, retinol intake was negatively associated with bone mineral density. For every l-mg increase in daily intake of retinol, risk for hip fracture increased by 68% (95% CI, 18% to 140%; P for trend, 0.006). For intake greater than 1.5 mg/d compared with intake less than 0.5 mg/d, bone mineral density was reduced by 10% at the femoral neck (P = 0.05), 14% at the lumbar spine (P = 0.001), and 6% for the total body (P = 0.009) and risk for hip fracture was doubled (odds ratio, 2.1 [CI, 1.1 to 4.0]). Conclusion: High dietary intake of retinol seems to be associated with osteoporosis.